Differential inflammatory response dynamics in normal lung following stereotactic body radiation therapy with protons...

To compare time-dependent changes in lung parenchyma of early-stage non-small cell lung carcinoma (NSCLC) patients after stereotactic body radiation therapy with protons (SBPT) or photons (SBRT).

We retrospectively identified NSCLC patients treated with SBPT and matched each one with a SBRT patient by patient, tumor, and treatment characteristics. Lung parenchyma on serial post-treatment chest computer tomography (CT) scans was deformably registered with the treatment plan to analyze lung density changes as function of dose, quantified by Houndsfield Unit (HU)/Gy. A thoracic radiologist also evaluated the CTs using an established grading system.

We matched 23 SBPT/SBRT pairs, including 5 patients treated with both modalities (internally matched cohort). Normal lung response following SBPT significantly increased in the early time period (CTs acquired <6 months, median 3 months) post-treatment, and then did not change significantly in the later time period (CTs acquired 6-14 months, median 9 months). For SBRT, the normal lung response was similar to SBPT in the early time period, but then increased significantly from the early to the late time period (p = 0.007). These differences were most pronounced in sensitive (response >6 HU/Gy) patients and in the internally matched cohort. However, there was no significant difference in the maximum observed response in the entire cohort over all time periods, median 3.4 [IQR, 1.0-5.4] HU/Gy (SBPT) versus 2.5 [1.6-5.2] HU/Gy (SBRT). Qualitative radiological evaluation was highly correlated with the quantitative analysis (p < 0.0001).

While there was no significant difference in maximum response after SBPT versus SBRT, dose-defined lung inflammation occurred earlier after proton irradiation. Further investigation is warranted into the mechanisms of inflammation and therapeutic consequences after proton versus photon irradiation.